Document Xzav0m9vEDB37Q2M6MRa0rODJ

HtufiiiVUal B f O - T E S T Xahiai&'im, Dnc. o REPORT TO . MONSANTO COMPANY TWO-YEAR CHRONIC ORAL TOXICITY WITH AROCLOR 1260 IN ALBINO RATS NOVEMBER 12, 1971 EBT NO. B7298 I. Introduction At the request of Monsanto Company, a two-year chronic oral toxicity study was conducted using albino rats to determine the potential toxicity of Aroclor 1260, Lot No. AK-3. The following report presents the results of this investigation. * DSW 034115 STLCOPCB4017939 DnktuVual B I O T E S T laloiabyu&L. Dho. 2 II. Summary A two-year chronic toxicity study was conducted using albino rats fed diets containing 1 (T-I), 10 (T-II), or 100 (T-III) ppm Aroclor 1260. Food consumption and body weight gains were not altered at any level of Aroclor 1260 fed. The number of animals dying and the time at which the deaths occurred did not vary among the test and control groups. Hematological and clinical blood chemistry studies conducted after 3, 6, 9, 12, 18, or 24 months did not reveal any affects related to Aroclor 1260. Urine analyses failed to reveal any differences between test and control animals. i At sacrifice after 3, 6, or 12 months on test organ weights, organ to body weight and organ to brain weight ratios disclosed several randomly occurring intergroup differences. The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences were not related to the ingestion of Aroclor 1260. At the final sacrifice after 24 months on test, the liver weights and liver to body weight or brain weight ratios were significantly elevated in the rats from the T-III group. Histologic examination of the livers from the T-IH group revealed several animals with vacuolar change. This lesion is morphologically indicative of fatty degeneration. Specific fat stains confirmed the presence of fat in these vacuoles. Focal hypertrophy and focal hyperplasia were also found in the livers from animals fed Aroclor 1260. osw 034116 STLCOPCB4017940 UndttibUal B I O - T E S T JaltMaUiid, Dm. 3 Hyperplasia of the urinary bladder was found in an animal from the control group but not in any of the test animals. The incidences and types of all tumors were about the same in all groups, including the control group, and are considered normal for rats of this age. Respectfully submitted, INDUSTRIAL BIO-TEST LABORATORIES, INC. Report prepared by: PhilipP Smith, B. S. Assistant Toxicologist Rat Toxicity Report approved by: James B. Plank Settlor Group Leader Rat Toxicity Mt JL,. Keplirfg^ Manager, Toxicology November 12, 1971 lamjsjn DSW 034117 STLCOPCB4017941 Undliiltial B I O - T E S T Xa&MaioMcA, 9nc. ! 4 III. Procedure i A. Experimental Animals The animals employed in the test were Charles River strain* albino rats. Four hundred rats (200 males and 200 females) were selected for the experiment, ear-punched with the animal number assigned and housed individually in standard wire-bottomed steel rat cages. Each cage bore a color-coded card identifying the rat with re spect to project number, dose level assignment, individual animal number and sex. B. Organization of Groups A structural outline of the experiment is given in Table I. TABLE I TEST MATERIAL: Aroclorl260 Two-Year Chronic Oral Toxicity Study - Albino Rats ' Outline of Experiment Group Control Number of Animals Male Female 50 50 Dietary Level (ppm) None Administered T-I 50 50 ' 1 T-II 50 50 . 10 T-III 50 50 100 * Charles River Breeding Laboratories, North Wilmington, Mass. . DSW 034118 STLCOPCB4017942 DfubiiUlal BIO-TEST ^ahyiaio-tici., Unc. / 5 C. Diets, Feeding and Food Consumption All diets were prepared in the central diet room of this laboratory. The basic ration from which all diets were constructed was a standard, pulverized stock rat ration*. The diet for any given test group was prepared by blending the calculated amount of Aroclor 1260 with a pre-weighed portion of the stock ration in a Hobart mixer. Fresh diets were prepared each week and every rat was offered an amount of food sufficient for cid libitum feeding. Food consumption was recorded for five rats of each sex in every group weekly for the first three months and monthly for the next nine months. Thereafter, periodic spot checks were made. ' D. Body Weights and Weight Gains Initially, the body weight of each rat in every group was deter mined and recorded. Thereafter, individual weighings were made weekly for the first 13 weeks and monthly thereafter until the conclusion of the investigation. , E. Mortality and Reactions Checks for mortality and abnormal behavioral reactions were made daily throughout the investigation. F. Hematologic Studies and Urine Analyses Blood studies, including determinations of hemoglobin concentra tions, hemotocrit value, erythrocyte count and both total and differential DSW 034119 * Purina Rat Chow, Ralston Purina Co. , St. Louis, Mo. STLCOPCB4017943 Pndn'iiMal BIO-TESY Xabyiai&'Uei, 9nc. <D 6 leukocyte counts, were conducted upon five males and five females from both the control and 100 ppm groups. Urine analyses for the presence of glucose, albumin, micro scopic elements, and determinations of pH and specific gravity were con ducted upon urine samples at the same time intervals and from the same animals as those employed for the blood studies. These studies were conducted after 3, 6, 9, 12, 18, and 24 months of feeding. G. Clinical Blood Chemistry Studies Determinations of blood urea nitrogen concentration (BUN), serum alkaline phosphatase activity (SAP), fasted blood glucose concen tration and serum glutamic-pyruvic transaminase activity (SGPT) were conducted after 3, 6, 9, 12, 18, and 24 months of feeding upon the same rats as were the routine blood studies. H. Pathologic Studies When an animal succumbed during the test period, a gross autopsy was performed. In those cases when postmortem autolysis was not ad vanced, representative tissues were taken and preserved in ten percent formalin solution for possible future histopathologic study. After 3, 6, and 12 months of testing, five animals of each sex from each group were sacrificed and subjected to complete gross pathologic examinations. DSW 034120 STLCOPCB4017944 Dtutkiitial B I O - T E S T J.alvyiaU'uei; Due. Y 7 Absolute organ weights were recorded and organ to body weight and organ to brain weight ratios computed. The following organs were included: liver, kidneys, spleen, gonads, heart and brain. These data were then subjected to statistical analysis. An Analysis of Variance was conducted first and significant effects disclosed by that treatment were further studied by "t"-tests. Complete microscopic examinations were conducted upon the tissues and organs from all control and 100 ppm group rats sacrificed s after 3, 6, or 12 months of testing. The following tissues and organs were included in the examinations: heart, trachea, lungs, liver, pancreas, esophagus, stomach, small intestine (duodenum, jejunum and ileum), caecum, colon, spleen, lymph nodes, kidneys, urinary bladder, gonads, prostate gland, seminal vesicles, uterus, pituitary gland, adrenal glands, salivary glands, thyroid gland, parathyroid glands, skeletal muscle, sternum, bone, peripheral nerve, spinal cord and brain (cerebrum, cerebellum and pons). . . * The aforementioned tissues were prepared and stained with Hematoxylin-Eosin stain. After two years of feeding, all surviving animals were sacrificed and subjected to complete gross pathologic examination. The absolute weights of the liver, kidneys, spleen, gonads, heart and brain were recorded immediately after sacrifice. DSW 034121 STLCOPCB4017945 Unduikial B I O - T E S T XaltO'iato'Ucl, Dnc. /i 8 Microscopic examinations were conducted upon tissues and organs from selected animals dying during the experiment and upon all animals from the final sacrifice. Tissues and organs examined were the same as those previously mentioned, I, Tumor Incidence and Classification A tabulation of the incidence of tumor formation in each group was made at the conclusion of the investigation. In addition, tumor data for individual animals including location, weight, size and pathologic classification were recorded. i OSH 034122 STLCOPCB4017946 QndiiiOUal B I O - T E S T Xal&'iah'Uvl, 9nc. 9 IV. Results A. Body Weights and Weight Gains The male and female body weight data are assembled in Table II. The data in this table also include the 3, 12 and 24 month total weight gains. There were no significant effects due to ingestion of the compound // l DSW 034123 STLCOPCB4017947 SI 3 1 * O I 3 H 'W ' O TABLE n TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Body Weight and Total Weight Gain Data Summary of Mean Values etary Level of vroclor 1260 (ppm) Sex Body Weight 90-Day (grams) Total Weight Week: Gain 0 1 2 3 4 5 6 7 8 9 10 11 12 13 (grams/rat) >ntrol M 'F 133 203 245 313 362 373 391 409 424 440 440 449 467 474 136 178 190 219 244 254 259 265 270 276 281 278 290 288 341 152 1 M 133 192 250 322 361 374 394 416 428 448 450 474 479 490 357 F * 136 167 189 218 241 252 256 261 268 273 277 281 290 288 152 10 M 133 204 245 317 368 382 400 417 436 448 461 467 475 481 348 F 136 174 190 217 242 254 260 263 268 274 281 279 285 288 152 100 M 133 208 247 319 363 375 394 425 437 451 460 479 486 500 367 F 136 173 188 222 240 253 258 262 265 267 270 275 275 280 144 STLCOPCB4017948 CDo oo OJ tv & \ u D iuLdbuoL B I O - T E S T J a /ta 'ta k i' i& i, Due. STLCOPCB4017949 9 )ietary Level of Aroclor 1260 (ppm) Sex Control M F 1 .M F 10 M F 100 . M F TABLE II continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Body Weight and Total Weight Gain Data Summary of Mean Values 45 6 498 533 297 310 565 322 516 547 578 298 307 314 496 526 ' 551 291 306 *314 522 555 580 289 302 307 Body Weight (grams) Month: `7 8 9 593 622 642 333 345 359 600 628 643 321 333 340 581 606 633 331 340 358 607 633 650 314 326 333 10 11 667 688 374 383 668 688 353 367 660 685 370 381 '681 342 707 347 9 12-Month Total Weight Gain 12 (grams/rat) 701 568 390 254 699 J 379 566 243 709 576 388 252 717 584 363 227 oCXo o *-* f\J ui si a i - o 19 v w f ' w c Qo TABLE II continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Body Weight and Total Weight Gain Data Summary of Mean Values .etary Level of \roclor 1260 (ppm) Sex mtrol M 'F 1 M' F 10 M F 100 M F - 13 14 15 16 728 746 759 768 426 444 466 481 721 740 760 768 390 427 466 433 728 745 776 . 761 416 434 482 449 746 760 772 775 380 386 417 414 Body Weight (grams) Month: 17 18 19 20 769 767 760- 758 500 515 533 547 776 774 762 753 445 476 481 493 768 780 774 761 473 508 519 530 774 769 760 750 435 453 471 481 21 22 739 726 551 550 733 718 514 530 735 715 536 542 733 714 500 507 24-Month Total Weight Gain 23 24 (grams / rat) 687 642 564 551 715 654 484 525 509 415 521 385 683 645 536 584 711 641 485 537 512 . 448 508 401 STLCOPCB4017950 o<s, x: o ts U> t-- (V O' V Ptidtfifrual B I O - T E S T ^aioAaixiici, 9hc. /s 13 B. Food Consumption The data obtained from the food consumption measurements conducted during the first 12 months of feeding are summarized in Table HI. These data revealed no significant difference between test and control rats. The periodic checks conducted during the remainder of the investigation also revealed no outstanding differences between test and control animals. i DSW 034127 STLCOPCB4017951 TABLE HI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Food Consumption Data O m to Summary o Mean Values Food Consumption ry Level of (gr ams/rat/seven days) Average Food >clor 1260 Week: Consumption (ppm) Sex 1 2 3 4 5 6 7 8 9 10 11 12 13 (grams/rat/seven davs Control M 94 160 175 163 137 137 225 197 204 188 191 194 196 F 73 140 144 107 104 133 208 154 165 151 146 150 151 174 140 1 M 118 154 151 169 201 116 200 193 201 193 189 187 194 F 95 118 97 139 160 107 162 139 165 149 150 143 147 10 M 106 146 144 142 190 136 196 214 214 192 191 199 200 F 94 124 128 124 179 90 190 167 155 151 150 149 152 175 136 * 175 143 ioo M 121 150 156 117 187 124 121 190 196 186 184 199 189 F 89 93 123 151 151 101 193 136 140 144 144 147 146 163 135 C/> H 1" DCo X Oo o0 o US)' 00 fSJ o Oo vl CO OIs)l . X Cv IhuiulU ial B I O - T EST STLCOPCB4017953 Oo stary Level of .roclor 1260 (ppm) Sex 4 Control M 196 F 148 1 M 196 F 148 10 M 186 F 142 100 M 179 F 156 TABLE III continued TEST MATERIAL: Arodor 1260 ' Two-Year Chronic Oral Toxicity Study - Albino Rats Food Consumption Data Summary of Mean Values Food Consumption (grams/rat/seven days) Average Food Month: Consumption 5 6 7 8 9 10 11 12 ferams/rat/seven days) 189 168 ' 147 163 184 179 170 187 154 136 121 138 152 160 141 127 176 142 200 189 192 179 181 182 172 184 163 141 163 160 153 157 143 132 191 . 188 * 193 197 197 168 164 196 138 145 144 144 151 136 139 141 186 151 . 186 142 170 180 188 186 166 181 188 180 127 147 144 134 132 162 149 139 ` 180 143 o c/o s: o w i--*- rvi sO 9tdhalrUal B I O - T E S T Jakyiato'iiM, 9nc. 16 C. Mortality and Reactions A frequency distribution of natural deaths occurring during the investigation appears in Table IV. No untoward behavioral reactions were noted among any of the animals employed in the investigation. I DSW 034130 STLCOPCB4017954  ou{ '-MLvpnofDf 1 S 3 JL* O I a p n y w rfrc Dietary Level (ppm)Sex 1-3 Control M F 1M F. 10 M F 100 M F TABLE IV TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rate Mortality Data Frequency Distribution of Deaths Frequency Distribution of Deaths Months: . 4-6 7-9 10-12 13-15 16-18 19-21 0 00 2 1 76 000 1 3 57 0 01 1 4 75 0 00 2 3 3 6 1.1 0 0 0.0 2 3 47 24 8 5 1 00 0 22 2 0 2 3 86 57 22-24 9 3 8 5 6 3 9 4 Total Dead Number Tested* 25/35 19/35 26/35 19/35 29/35 ' 17/35 29/35 23/35 # Does not include the five animals of each sex from every group sacrificed for interim pathologic studies. STLCOPCB4017955 oin X o IP F*- VP thultiit'iial B I O T E S T Jtahyiaityiiel, Due. 18 D. Hematologic and Clinical Blood Chemistry Studies Mean male and female hematologic and clinical blood chemistry data are summarized in Tables V through IX. Values for all parameters investigated were within the normal range for the albino rat. No significant differences between test and control values were observed. i DSW 034132 STLCOPCB4017956 Dwsudinial B i O - T E 5 T la l& ia l& iic i, Dhc. STLCOPCB4017957 Dietary Level (ppm) Control Sex 3 M 14.0 F 9. 1 TABLE V TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Hematologic Data Summary of Mean Values Total Leukocyte Count (thousands/ mm^) Month: 6 9 12 18 ..... 24 .Erythrocyte Count (millions/mm^) Month: 36 9 12 18 15.4 10.1 11. 1 9.9 11.2 8. 1 8.2 8. 7 8.8 7.6 9.4 6.7 7.6 8.8 7.6 . 7. 5 7.7 7. 3 7.8 7. 7 24 6.5 6.8 M 10.8 13.1 7.9 12. 8 8.6 8.4 100 F 13.2 8.2 7.9 * 6. 5 7. 8 7.4 7. 5 8. 1 8.0 7.6 8.0 7.6 7. 3 7.5. 7. 3 7.5 7. 4 6.4 o <s> sc o t-- U> NO OJ h 1 s 3 1 O I a' Dietary Level <PPm) Control Sex M F 3 17. 1 16.9 Q TABLE VI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Hematologic Data Summary of Mean Values Hemoglobin Concentration (g/100 ml) Month: 6 9 12 18 24 Hematocrit Value {%) Month: 3 6 9 12 17.7 15.7 17.6 16. 1 13.6 51 49 48 50 17.4 14.1 16.7 16.4 14.6 50 47 43 46 9 18 24 41 35 42 38 M 16.1 17. Z 14.0 15. 3 15.9 14.5 100 ' F 16.3 17.0 13. 7 . 15.6 15.3 12.9 49 47 43 43 41 38 48 47 41 44 39 32 oufi STLCOPCB4017958 Vsoc o Uj U) Otv* b Tv j. s 3 1 * O l 9 eo Dietary Level (ppm) Control Sex 3 M 82.0 F 83.0 TABLE VH TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Hematologic Data Summary of Mean Values Differential Leukocyte Count (Number of Cells per Hundred) Lymphocytes Neutrophils Month: Month: 6 9 12 18 24 3 6 9 12 18 24 86. 6 80.4 . 78.8 79.0 65.4 16.0 11.4 18.6 20.6 20.0 32. 2 86. 6 86. 8 89.0 70.2 61.4 15.4 11.6 11.8 10.0 29.2 36. 0 M 85. 8 85. 4 83.4 72. 4 73. 8 66.6 100 F 92.0 89.6 78. 8 * 82.2 80.6 65.6 12.6 13.8 15.8 22.6 24.6 31/6 7.6 10.0 19.4 17.0 17.4 34.2 o (/> s: o u> ** bJ STLCOPCB4017959 I aA tw ypw for 1 s 31 - O I 8 Dietary Level (ppm) Control Sex 3 M 0.6 F 0.6 M 0.0 100 F 0.0 O TABLE VII continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Hematologic Data Summary of Mean Values Differential Leukocyte Count (Number of Cells per Hundred) Monocytes Eosinophils Month: Month: 6 9 12 18 24 3 6 9 12 18 24 0.0 0.0 . 0.4 0. 2 1.2 1.4 2.0 1.0 0.2 0. 8 1.6 0.0 0. 0 0.0 0. 2 1.0 1.0 1. 8 1.4 0. 2 0.6 1.6 0.0 0.0 0.0 0.4 0. 8 0.0 0.0 0.0 0.4 0.2 1.4 0. 8 1.0 1.2 . 1.0* 0.4 0.4 0.8 1.6 0. 0 o GO X o r-UJ O' Cv CO o 00 o STLCOPCB4017960 JU UntitUiAial B IO -T E S T J.aJxy\aiiyiipA, Dnc. STLCOPCB4017961 Dietary Level (ppm) Control 100 Sex M F M F o Us o b*-* OJ si TABLE VII continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Hematologic Data Summary of Mean Values Differential Leukocyte Count (Number of Cells per Hundred) Basophils Month: 36 9 12 18 0.0 0.0 0. 0 0. 0 0. 0 0.0 0.0 0.0 0.0 0.0 0.2 . 0.0 0.0 0.0 0.0 0.0 * 0.0 0. 0 0.0 0.0 24 0.0 0.0 0.0 0.0 Wtvi L r V is 3 1 -O ia W W Dietary Level (ppm) Control Sex 3 M 38 F 33 100 M 33 F 29 TABLE Vni TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Clinical Blood Chemistry Data Summary of Mean Values Serum Glutamic-Pyruvic Transaminase Activity (Dade Units) Month: 6 9 12 18 24 36 Blood Urea Nitrogen Concentration (mgs %) Month: 9 12 18 24 48 45 45 42 36 17 15 12 10 14 15 39 38 42 32 30 14 16 15 9 13 11 39 42 . 43 31 36 37 50 40 32 33 14 15 17 16 16 15 15 15 14 13 12 14 o ts> at o OJ a H&AiciJAial B I O - T E S T Dietary Level (ppm) Sex 3 M 128 Control F 130 M 118 100 F 117 TABLE EX TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Clinical Blood Chemistry Data Summary of Mean Values Fasted Blood Glucose Concentration (mgs%) Month: 6 9 12 18 24 Serum Alkaline Phosphatase Activity (King-Armstrong Units) Month: 3 6 9 12 18 24 123 89 88 138 99 28.6 24. 7 21. 5 20. 3 16.2 22.3 118 115 92 134 109 18.9 17. 8 10.6 11.9 16. 8 20. 2 00 H 118 116 . 135 146 98 116 115 138 146 94 37.8 12.0 12. 1 21. 9 7.6 23. 9 11.7 11. 9 7.8 16. 1 12.4 Unc. STLCOPCB4017963 D in a: c u> VcvI U) SO x> ?*ubtihial B I O T E S T Ja&y'iaimet, 9nc. 26 E. Urine Analyses Mean male and female urine analyses data are summarized in Tables X through XII. Determinations for glucose concentration were negative for all rats at every interval of examination. No differences were noted between the urine from control and test animals at the intervals of examination. A(f i DSW 034U0 STLCOPCB4017964 0'Duduibual B 1 - T E S T J.alfO-'iahyiiei-, Dhc. STLCOPCB4017965 Dietary Level (PPm> Control Sex 3 Mn Fn Mn 100 Fn TABLE X TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Urine Analyses Data Summary of Mean Values Glucose Month: 6 9 12 nnn nnn 18 24 nn nn Albumin Month: 3 6 9 12 18 24 n n t t +2 + 3 nnnnt +2 n n n nn n n n nn n t t t + 1 +3 n n . n n + 1 +4 Key: n = negative t = trace; less than 30 mg/100 ml urine + 1 = 30 to 100 mg/100 ml urine + 2 = 100 to 300 mg/100 ml urine + 3 = 300 to 500 mg/100 ml urine + 4 = more than 500 mg/ 100 ml urine . * tv> --t DSW 034141 Dietary Level (ppm) Control Sex 3 MN FN MN 100 FN TABLE XI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Urine Analyses Data Summary of Mean Values Microscopic Elements Month: 6 9 12 18 NN N N NNNt 24 +1 t pH Month: 3 6 9 12 18 24 7 76 776 8 8 7 86 6 N N N Nt N N N tt 7 7 6 76 6 7 86 766 Key: N= Normal t = trace; less than 5 per low power field +1 = 5 to 10 per low power field + 2 = 10 to 15 per low power field + 3 = more than 15 per low power field _ DSW 034142 StuhtibUol B I O - T E S T Xab&'icdtvUei, Snc, Nl 00 0StuififhuU B I - T E S T Xalt&iaityUel, Hoc. STLCOPCB4017967 O Dietary Level (ppm) .t Control J *. 100 Sex M F M F TABLE XU TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Urine Analyses Data Summary of Mean Valuea 3 1.029 r ,, 1.020 fr 1.021 r' . 1.016 6 f, . 1.022 r i 1.019 1.025 1.023 Specific Gravity Month: 9 12 1.033 1.027 1.025 1.024 *1 1.031 1. 035 ' 1.030 t 1.029 18 1.042 1.032 1.043 1.028 24 1.051 ' 1.039 1.039 * 1.045 o CO X o tv fr-- OJ B I O - T E S T J.alvy>iatoAici, 9nc. 30 F. Pathologic Studies Three-Month Sacrifice a. Gross Pathologic Findings No outstanding differences were noted between test and control rats upon gross pathological examination. b. Organ Weight and Organ to Body and Organ to Brain Weight Ratio Data The results of the statistical analyses conducted on absolute organ weights, organ to body weight and organ to brain weight ratios are summarized in Tables XIII through XVIII. Significant differences between a test group and the control group are designated by asterisks following the test values. Organ weights, organ to body weight and organ to brain weight ratios disclosed several randomly occurring intergroup differences. The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences were not related to the ingestion of Aroclor 1260. DSW 034144 STLCOPCB4017968 HndM foial B I O - T E 5 T la&y-iaionicS, Hue. STLCOPCB4017969 O '* Dietary Level of Aroclor 1260 (ppm) Control 1 10 100 e TABLE XHI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Values Organ: Liver . ' . Organ Weight (g) Males Females 21.4 13.0 20.4 1*3.2 24.0** 12.2 29.5** 14.5 Organ/Body Weight Ratio (g/100 g) Males Females 4.13 4. 16 3.90 4.59 4.48 3.61 - 5.73** 4.58 Organ/Brain Weight Ratio (g/g) Males F emales 10.3 6.82 9.98 6.86 11.8 6.38 14.4** 7.72 oV) * Statistically significant difference at the 99 percent confidence level ou> S' t-* USl' G / STLCOPCB4017970 Dietary Level of Aroclor 1260 (ppm) . Control l 10 100 o in at o U) (-* f' O' TABLE XIV TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Values Organ: Kidneys Q Organ Weight <g) Males Females 4.03 2.49 4.37 2.62 4.00 2.61 4.00 2.52 Organ/Body Weight Ratio (g/100 g) Males Females 0.782 0.802 0.838 0.911 0.747 0.782 0.779 0.793 Organ/Brain Weight Ratio (g/g) Males Females 1.95 1.31 2.14 1.36 1.96 1.37 1.96 1.35 `OUfi yavwrfcuvifop S 3 1 * O ! Si u* tv u STLCOPCB4017971 TABLE XV TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Values Organ: Spleen Dietary Level . of Organ Weight Organ/Body Weight Ratio Organ/Brain Weight Ratio Aroclor 1260 (g) (g/100 g) (g/g) (ppm) Males______________________FemalesMalesFemales ________ Males_______ Females Control 0.766 0.578 0.150 0. 184 0.371 0.302 1 0.846 0.516 0. 161 0.180 . 0.412 0.269 10 0.838 0.632 0.156 0.189 0.411 0.331 100 0.718 0.556 0. 140 0. 177 0.352 0.297 C3 IS> o IP si 3 I ' O I 9 fW fnyw S U STLCOPCB4017972 % Dietary Level of Aroclor 1260 (ppm) Control 1 10 100 o X o CD QQ TABLE XVI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Values Organ: Gonads . . .* . Organ Weight (g) Males Females 3.60 0.114 3.67 0.128 3.83 0.121 3.71 0.138 Organ/Body Weight Ratio (g/100 g) Males Females 0.698 0.0370 0.704 0.0450 0.715 0.0368 0.725 0.0429 Organ/Brain Weight Ratio (g/g) Males Females 1.74 0.0599 1.80 0.0666 1.89 0.0636 1.81 0.0728 rw y m & fD f 1 s 3 * O I 3i c- f\ D ndyifoial B I O - T E S T Xak&'iaio-'iici; 9nc. STLCOPCB4017973 Dietary Level of Aroclor 1260 (ppm) Control 1 10 100 oixn oui TABLE XVII TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Values Organ: Heart Organ Weight (g) Males Females 1.59 1.57 1.05 1.01 1.58 1.52 1.04 0.946 Organ/Body Weight Ratio (g/100 g) Males Females 0.307 0.300 0.339 0.353 0.296 0.311 0.298 0.297 Organ/Brain Weight Ratio (g/g) Males Females 0.767 0.551 0.765 0.526 0.781 0.743 0.546 0.505 U> Cm N> STLCOPCB4017974 Dietary Level . of Aroclor 1260 (ppm) Control 1 10 100 CJ (S> SC oU) U1 o 'r w y v w } 0? 1 S 3 X O I 9' O TABLE XVIII TEST MATERIAL: Aroclor 1260 Two-Tear Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Values Organ: Brain Organ Weight (g) Males Females 2.07 2.05 1.91 1.92 2.04 2.05 1.91 1.89 Organ/Body Weight Ratio (g/100 g) Males Females 0.402 0.616 0.392 0.672 0.380 0.572 0.400 0.593 Final Body Weights of Sacrificed Rats (g) Males Females - 518 314 523 287 536 337 517 321 u> o Ow dn6faial B I O - T E S T J^altosiaioAici., 9tic. 37 c. Histopathologic Findings Histopathologic examination of tissues and organs taken from all animals from both the control and 100 ppm groups was conducted. Tables XIX and XX list all histopathologic changes noted. All of the lesions noted in the microscopic examina tion of tissues were those of spontaneous disease and are not unusual for the albino rat. The most frequent findings were lesions in the trachea and lungs, indicating chronic murine pneumonia. These oc curred in the control as well as the rats fed Aroclor 1260. i 3f OSW 034151 STLCOPCB4017975 . Sn<iniViial B l O - T E S T latmlahyiioi-, 9nc. 38 O TABLE XIX TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes ' Three-Month Sacrifice Group: Control Nu*m ber of Animals Organ Examined Findings 5 Males Trachea Lung Urinary bladder Tracheitis Chronic respiratory disease Hyperplasia 5 Females Lung Chronic respiratory disease Ave rage Incidence Grade 1 1.0 1 1.0 3 1.0 ! 1 1.0 All other tissues and organs were normal histologically. Grading System 0.5 = minimal 1.0 = slight 2.0 = mild 3.0 = moderate 4.0= severe 5.0 = extreme O OSW 034152 STLCOPCB4017976 . Ctuhuhial B I O - T E S T Jalw-'iattvucd, 9nc. I 39 TABLE XX TEST MATERIAL; Aroclor 1Z60 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes ' Three-Month Sacrifice Group; 100 ppm Number of Animals Organ Examined Findings 5 Males Trachea Lung Tracheitis Chronic respiratory disease 5 Females T rachea Lung Kidney Tracheitis ' Chronic respiratory disease Focal lymphoid infiltration Average Incidence Grade 4 1.0 2 1.0 ' 3 1.0 2 1.0 1 1.0 All other tissues and organs were normal histologically. Grading System ' 0.5 = minimal 1.0 = slight 2.0 = mild 3.0 = moderate 4.0= severe 5.0 = extreme ' DSW 034153 STLCOPCB4017977 . PnduilAial B 1 O - T E S T laluyiaiaxiel, Hhc. 40 2. Six-Month Sacrifice a. Gross Pathologic Findings No outstanding differences were noted between test and control animals. ' b. Organ Weight and Organ to Body and Organ to Brain Weight Ratio Data The results of the statistical analyses conducted on absolute organ weights, organ to body weight and organ to brain weight ratios are summarized in Tables XXI through XXVI. Organ weights, organ to body weight and organ to brain weight ratios disclosed several randomly occurring intergroup differences. ! The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences were not related to the ingestion of Aroclor 1260. o DSW 034154 STLCOPCB4017978 sw# 'fW tf/w yry- 1 S 3 1 o I 9 J W lP 'p ty '' TABLE XXI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values Organ: Liver . Dietary Level of Aroclor 1260 (ppm) Control Organ Weight (g) Males Females 22.9 13.1 Organ/Body Weight Ratio (g/100 g) Males Females 3.74 3.77 Organ/Brain Weight Ratio (g/g) Males Females 11.7 6.71 1 14.8** . 15.1 2.92** 3.74 7.05** 7.86. 10 19.0* 10.5** 3.31* 3.08* 9.45* 6.07 100 24.4 11.6 4.69* 4.03 D (A SC * Statistically significant difference at the 95 percent confidence level. o ** Statistically significant difference at the 99 percent confidence level. OJ t-- U1 U1 12.3 6.17 STLCOPCB4017979 5 S ttduifaial B l O - T E S T Xa&o-ialviic-. STLCOPCB4017980 Dietary Level of Aroclor 1260 (ppm) Control 1 10 100 TABLE XXII TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values . Organ: Kidneys e Organ Weight (g) Male3 Females 4.04- 2.79 3.64 2.73 3.85 2.35 3.92 2.35 Organ/Body Weight Ratio (g/100 g) Males Females 0.664 0.806 0.716 0.674* 0.670 0.684* 0.753 0.814 Organ/Brain Weight Ratio (g/g) Males Females 2.06 1.43 1.73 1.42 1.92 1.36 1.97 1.25 * Statistically significant difference at the 95 percent confidence level. a u> SC o Ijj *-* O' O' r fM tu d BIO -TEST OSW 0 3 4 1 5 7 Dietary Level o Aroclor 1260 (ppm) Control 1 * 10 100 TABLE XXin TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Six-Month Sacrifice ' Summary of Mean Values Organ: Spleen Organ Weight (g) Males Females 0.752 0.684 0.754 6.908 0.836 0.566* 0.636 0.443* Organ/Body Weight Ratio (g/100 g) Males Females 0.122 0.196 0.148** 0.220 0.146* 0.167 0. 122 .0.151 Organ/Brain Weight Ratio (g/g) Males Females 0.384 0.350 0.359 0.472 0.416 0.327 0.320 0.236* s SVk' r * Statistically significant difference at the 95 percent confidence level. u> -oo 03 o -J <0 00 0\ 0jQ nJj'.iltial B I - T E S T Jla-La'uilji'iici-, STLCOPCB4017982 Dietary Level of Aroclor 1260 (ppm). Control 1 10 100 O TABLE XXIV TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ "Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values Organ: Gonads . o Organ Weight (g) Males Females 3.55 0.0960 3.23 (7.120 * 3.56 0.0968 3.53 0.0710* Organ/Body Weight Ratio (g/100 g) Males Females 0.593 0.0279 0.636 0.0297 0.620 0.0287 0.686 0.0250 Organ/Brain Weight Ratio (g/g) Males F emales 1. 81 0.0492 . 1.54 0.0625* 1.77 . .0.0560 1.77 0.0378* o * Statistically significant difference at the 95 percent confidence level. (/) x. o U) Vjo CO t <tK > Zndi'itnial B IO -T E S T STLCOPCB4017983 0 TABLE XXV TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values Organ: Heart Dietary Level of Aroclor 1260 (ppm) Organ Weight (g) Males Females Organ/Body Weight Ratio (g/100 g) Males Females Organ/Brain Weight Ratio (g/g) Males Females Control 1.70 1.05 0^282 0.302 0.867 0.538 1 1.45 T. 12 0.286 0.277 0.690 0.583 10 1.63 1.05 0.283 0.307 0.810 0.606 ICO 1.49 1.06 0.286 0.368** 0.749 0.564 o ** ** Statistically significant difference at the 99 percent confidence level. o. ip S' v**r* I t r U1 \4 STLCOPCB4017984 TABLE XXVI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values ' Organ: Brain Dietary Level of Aroclor 1260 Organ Weight (g) Males Females Organ/Body Weight Ratio (g/100 g) Males Final Body Weights of Sacrificed Rats (g) Control 1.96 1.95 0.320 0.560 613 348 1 2.10 *1.92 0.412* 0.474* 509 405 10 2.01 1.73 0.349 0.504 575 . 343 100 1.99 1.88 0.382 0.650* o (/> s: * Statistically significant difference at the 95 percent confidence level. oUI o o 522 289 WO `vniopnxyD f i s 3 i - 19o O' Is , SaJ^iAlal B l O - T E S T Ja&cnaiyuei, Stic. V? 47 c. Histopathologic Findings Histopathologic examination of tissues and organs taken from all animals from both the control and 100 ppm groups was conducted. Tables XXVII and XXVIII list all histopathologic changes noted. ' All of the lesions noted in the microscopic examination of tissues were those of spontaneous disease and are not unusual for the albino rat. The most frequent findings were lesions in the trachea and lungs, indicating chronic murine pneumonia. These occurred in the control as well as the rats fed Aroclor 1260. 1 DSW 034161 STLCOPCB4017985 . QtiJjtifoial B l O - T E S T Jahwak'UM, Due. r<j 48 TABLE XXVII TEST MATERIAL: Aroclor IZ60 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Six-Month Sacrifice Group: Control Number of Animals Organ Examined Findings Average Incidence Grade 5 Males Trachea Lung Liver Skeletal muscle Tracheitis Focal tracheitis Focal pneumonitis Hyperemia Focal pericholangitis Focal inflammation 2 2 1 2 ,1 1 1.5 1.0 0.5 1.0 1.0 1.0 5 Females Trachea Lung Liver Kidney Focal tracheitis Hyperemia Hype remia Pericholangitis Focal inflammation 1 1.0 2 2.5 1 1.0 1 0.5 1 1.0 All other tissues and organs were normal histologically. * Grading System 0.5 = minimal 1.0 = slight 2.0 = mild 3.0 = mode rate 4.0= severe 5.0 = extreme o DSW 034162 STLCOPCB4017986 Ptufuiklal B \ O - T E S T XaUvik'iict-, 9m. 49 j / TABLE XXVIII TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Six-Month Sacrifice Group: 100 ppm , Number of Animals Organ Examined Findings Average Incidence G rade 5 Males Trachea Lung Liver Tracheitis Focal tracheitis Focal pneumonitis Hyperemia Hyperemia Focal pericholangitis 2 1 4 4 1 2.0 0.5 1.0 1.5 1.0 0.5 5 Females T rachea Lung Liver Kidney Focal tracheitis Focal pneumonitis Hyperemia Hyperemia Focal pericholangitis Focal nephritis 2 2 1 2 1 3 0. 5 1.0 3.0 1.5 0.5 0.5 All other tissues and organs were normal histologically. Grading System 0.5 = minimal 1.0 = slight 2.0 = mild 3.0 = moderate 4.0 = seve re 5.0 = extreme DSW 034163 STLCOPCB4017987 . '^nduit^ial B I O - T E S T laJmah'U&i., Due. I 50 O 3. Twelve-Month Sacrifice a. Gross Pathologic Findings Gross pathologic findings among teet animals were not significantly different from those noted in control animals. b. Organ Weight and Ratio Data The mean organ weight and ratio data collected at the twelve month sacrifice are presented in Tables XXIX through XXXIV. Statistically significant differences are designated by asterisks following the test group value. Organ weights, organ to body weight and organ to brain weight ratios disclosed several randomly occurring intergroup differences. The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences were not related to the ingestion of Aroclor 1260. DSW 034164 STLCOPCB4017988 00 00* ot, fMWfPtofnp i $ 1 - i a 'o3 r ^ r c O Dietary Level (pom) Control 1 10 100 9 TABLE XXIX TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity- Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Values Organ: Liver Organ Weight (g) Males Females 22.1 15.5 17.1* 20.0 . 10.7* 13.6 14. 1 Organ/Body Weight Ratio (g/100 g) Males F emales 3.79 3.52 2.79** 3.01* 3.30 3.54 4.26 3.79 Organ/Brain Weight Ratio (g/g) Males Females 10.8 7.72 9.23 5.76 10.8 7.28 13.4* 8.52 * Statistically significant difference at the 95 percent confidence level. ** Statistically significant difference at the 99 percent confidence level. OSW 034165 KTt STLCOPCB4017989 a H uthiU iial B I O - T E S T Ja/tfria/oiicA, 9tic. STLCOPCB4017990 Dietary Level (ppm) Control 1 10 100 9 TABLE XXX TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats . Twelve-Month Sacrifice . Organ Weight and Ratio Data Summary of Mean Values Organ: Kidneys Organ Weight (g) Males Females 4.04 3.19 3.84 2.58** 4.00 2.7*8* 5.11* 2.81 Organ/Body Weight Ratio (g/100 g) Males Females 0.692 0.738 0.625 0.724 0.660 0.736 0.758 0.755 Organ/Brain Weight Ratio (g/g) Males F emales 1.97 1.58 2.06 1.39 . 2.16 1.48 2.38* 1.69 * Statistically significant difference at the 95 percent confidence level. ** Statistically significant difference at the 99 percent confidence level. oCXO ow *-* O' O' tv> V; X S 3 ' O I fli Q TABLE XXXI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Values Organ: Spleen Organ Weight Organ/Body Weight Ratio Dietary Level (g) (g/100 g) (ppm)MalesFemalesMalesF emalesMales Control 0.778 0.796 . 0.133 0.183 1 0.756 0.460* 0. 122 0.129* 10 0.836 . 0.578 0.139 0. 150 100 0.785 0.474* 0. 116 0.127* Organ/Brain Weight Ratio (g/g) Females 0.380 . 0.408 0.457 0.365 0.396 0.247* ` 0.308 0.284 ot't * Statistically significant difference at the 95 percent confidence level. STLCOPCB4017991 oCO oOJpJ- O' - b bulm hial B IO -T E S T STLCOPCB4017992 Q . Dietary Level fopTM) Control 1 10 100 QO TABLE XXXH TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Values . Organ: Gonads . Organ Weight (g) Males Females 3.46 0.116 3.38 3.51 0.103 0.1*12 4.03** 0.088* Organ/Body Weight Ratio (g/lOOg) Males Females Organ/Brain Weight Ratio (g/g) Males F emales 0.596 0.0275 1.70 0.0574 0.551 0.02 87 1.82 0.0552 0.578 0.0294 1.89 0.0584 0.598 0.0238 1.88 0.0527 * Statistically significant difference at the 95 percent confidence level. ** Statistically significant difference at the 99 percent confidence level. otA SE OUJ *-* O03 5B vn SnduiiAiaL B I O * T E S T jHa&aialo-iiC'i, 9nc. STLCOPCB4017993 Dietary Level (ppm) Control l 10 100 TABLE XXXIII TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Twelve-Month Sacrifice Organ. Weight and Ratio Data Summary of Mean Values Organ: Heart Organ Weight (g) . Males F emales 1.71 1.68 1.23 1.07 1.59 1.16" 1.86 1.27 Organ/Body Weight Ratio (g/100 g) Males Females 0.293 0.287 0.273 0.301 0.261 0.307 0.275 0.340 Organ/Brain Weight Ratio (g/g) Males F emales 0. 835 0.611 0.902 0.575 0.845 0.620 0.868 0.760 D </3 oO-FJ' VVII t--* O' N1 H h fL u kia l B I O T E S T lahyiafanlei., Dttc. STLCOPCB4017994 O Dietary Level (ppm) Control 1 10 100 TABLE XXXIV TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Twelve-Month Sacrifice Summary of Mean Values Organ Weight (g) Male 3Females Organ: Brain Organ/Body Weight Ratio (g/100 g) MalesFemales Final Body Weight of Sacrificed Rats (grams) Males Females 2.04 1.87 1.88 2.02 . 1.86 1.90 0.349 0.304 0.310 0.460 0.522 0.493 584 439 616 356 607 385 2.15 1.67** -0.318 0.449 675 372 ** Statistically significant difference at the 99 percent confidence level. c (/) X ou> S' osJ ' VO'I* Diuh'-itrial B I O - T E S T Jalo'iaio'u'cJ., 9hc. 57 c. Histopathologic Findings Histopathologic examination of tissues taken from each rat sacrificed from the control and 100 ppm groups after twelve months of testing was conducted. Tables XXXV and XXXVI list all hisopathologic changes noted. 'All of the lesions noted in the microscopic examination of tissues were those of spontaneous disease and are not unusual for the albino rat. The most frequent findings were lesions in the trachea and lungs, indicating chronic murine pneumonia. These occurred in the control as well as the rats fed Aroclor 1260. . DSW 034171 STLCOPCB4017995 DnJ/i-iiAlal B i O - T E S T J^alteAaieiieA., 9tic. &>C 58 TABLE XXXV TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Twelve-Month Sacrifice Group: Control . Number of Animals 5 Males 5 Females Organ Examined Trachea Lung , Urinary Bladder Trachea Lung Colon Findings Incidence Ave rage Grade Tracheitis Chronic respiratory disease Calculus 1 2 1 1.0 1.0 1.0 Tracheitis Chronic respiratory disease Parasites i1 1 1 1.0 1.0 1.0 All other tissues and organs were normal histologically. Grading System 0.5= minimal 1.0 = slight 2.0 = mild 3.0 = moderate 4.0= severe 5.0 = extreme OSW 0341?2 STLCOPCB4017996 StifhiAltial B I O - T E S T laluyiatb'U&i, 9nc. 59 TABLE XXXVI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Twelve-Month Sacrifice Group: 100 ppm Number of Animals 5 Males 5 Females Organ Examined Trachea Lung Kidney Liver Trachea Lung Findings Incidence Tracheitis Chronic respiratory disease Focal lymphoid infiltration Vacuolar change of random cells 1 3 1 ' 1 Tracheitis Chronic respiratory disease 1 1 Avc rage Grade 1.0 1.0 1.0 1.0 1.0 1.0 All other tissues and organs were normal histologically. Grading System 0.5 = minimal 1.0 = slight 2.0 = mild 3.0 = moderate 4.0 = severe 5.0 = extreme . DSW 034173 STLCOPCB4017997 !)futnAU<al B I O * T E S T Jalio-'iatMicd, Dhc, 60 4. Final Sacrifice a. Gross Pathologic Findings Gross pathologic findings among test animals were not significantly different from those noted in control animals. b. Organ Weight and Ratio Data The mean organ weight and ratio data collected at the final sacrifice are presented in Tables XXXVII through XL.II. Statistically significant differences are designated by asterisks following the test group value. Absolute liver weights and liver to body weight or liver to brain weight ratios were significantly elevated in those rats fed 100 ppm Aroclor 1260. Other organ weights, organ to body weight and organ to brain weight ratios disclosed several randomly occurring intergroup differences. The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences were not related to the ingestion of Aroclor 1260 DSW 034174 STLCOPCB4017998 STLCOPCB4017999 Dietary Level (ppm) Control 1 10 100 . TABLE XXXV n TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats . Organ Weight and Ratio Data 'i Summary of Mean Values Final Sacrifice Organ: Liver Org an Weight Males (g) Females 22.0 16. 3 Organ/Body Weight Ratio (g/ 100 g) Males Females 3.47 3.05 22.0 16.6 3.40 3. 35 24. 1 18. 1 2. 87* 3. 19 29.9** 22. 7#* 4.67** 4. 42** * Statistically significant difference at the 95 percent confidence level. Statistically significant difference at the 99 percent confidence level. oc/> c e Organ/Brain We ight Ratio (g/g) Males Females 10. 10 8.42 9.93 8.62 11. 20 9. 26 13.40* 11.60* o 15 3 1 *0 1 9 1 S 3 * O 10i O Dietary Level (ppm) Control 1 10' 100 TABLE XXXIX TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats . Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice ` Organ Weight Males (g) Females Organ: Spleen Organ/Body Weight Ratio (g/100 g) . Male s Female s 1. 15 .0.96 0. 182 0. 181 1. 17 1.09 0.72 0.83 0. 178 0. 131 0. 148 0. 142 0.89 0. 75 0. 138 0. 146 o Organ/Brain Weight Ratio (g/g) Males Females 0.520 0.492 0.529 0. 370 0.509 0.428 0.400 0. 379 `w f STLCOPCB4018000 oCr> SE O UJ wO t--vl O' vh O 9O HtuluilAial B I O T E S T J.ak>'uiio,Ucl, Shc. STLCOPCB4018001 . Dietary Level fppra) Control 1 10 100 TABLE XL TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats . Organ Weight and Ratio Data i Summary of Mean Values Final Sacrifice Organ: Gonads Organ Weight (g) . Males Females 2. 52 0. 123 Organ/Body Weight Ratio (g/100 g) Males F emales 0. 397 0.0222 3. 56* 0. 140 0. 550* 0.0317 3.36* 0. 177 0.400 0.0338 2.97 0. 113 0.464 0.0229 Organ/Brain Weight Ratio (g/g) Males Females 1. 15 0. 0628 1.61* 0.-0718 1.56* 0.0900 1. 33 0.0584 * Statistically significant difference at the 95 percent confidence level. oc/> O OJ si "si cr* IN 1 S 3 * O I 9 J w fV 'WI Dietary Level (ppm) Control 1 10 100 TABLE XLI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats . Organ Weight and Ratio Data l Summary of Mean Values Final Sacrifice Organ: Heart Organ Weight Males (g) Females 1. 87 1.54 Organ/Body Weight Ratio (g/ioo g) Males Females 0. 294 0. 288 1. 98 .1.45 0. 304 0. 294 1. 90 1. 58 0.225** 0. 279 2.00 1.49 0. 313 0. 288 ** Statistically significant difference at the 99 percent confidence level. Organ/B rain Weight Ratio (g/g) Males F emales 0. 860 0. 795 0. 893 0.747 0.884 0. 809 0. 904 0. 764 STLCOPCB4018002 o O 171 ow *"* oo BI O - T E S T JabMaityUol, Hue. STLCOPCB4018003 ' Dietary Level (ppm) Control 1 ' 10 100 TABLE XLB TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats . Organ Weight and Ratio Data i Summary of Mean Values Final Sacrifice ` Organ: Brain Organ Weight (g) Males Females Organ/Body Weight Ratio (g/lOOg) Males F emale Final Body Weight of Sacrificed Animals (grams) Males Females 2. 18 - 1.95 0.342. 0.362 642 551 2.21 2. 15 1.94 1.96 0.343 0.255** 0.407 0.347 654 845** 525 584 2. 22 1.95 0. 346 0.378 641 644 ** Statistically significant difference at the 99 percent confidence level. oO' Nj Ptidnii'ikil BIO-TEST JtaJ^yiaiyuei, 9tic. 67 c. Histopathologic Findings Histopathologic examination of tissues and organs taken from all animals sacrificed after 24 months on test was conducted. Tables XLIII through Xl/VI list all histopathologic changes noted.' Table XL.VII contains the results of the histopathologic examination of the urinary bladders. ` Significant liver injury was found in animals fed 100 ppm Aroclor 1260 (T-III). The compound associated lesions consisted of vacuolar change, focal hypertrophy and focal hyperplasia. In addition, there were lesions of inflammation, necrosis, fibrosis and minor degeneration in this group which, although seen in the controls and lower test groups, were more severe and frequent in the T-III group. The vacuolar change w^s not seen in the control animals but was observed occasionally in livers from T-I (1 ppm) and T-II (10 ppm) animals. It was frequent in the T-III animals. This lesion is morphologically indicative of fatty degeneration. Formalin-frozen sections of livers from represenative animals which displayed vacuolar changes were stained with Oil Red 0 to reveal the presence of fat. The vacuolar lesion in the cytoplasm of these cells was positively identified as fat. The hypertrophic change found in the liver was focal and often limited to the central lobular area where groups of cells were swollen to two or three times their normal size with clear pink homogenous cytoplasm. The hyperplasia was associated with the same cells and appeared to be an ' DSW 034180 STLCOPCB4018004 Dfiduihial B l O - T E S T Ja^aiaiici, 9etc. 68 extension of the hypertrophic lesion. The hyperplastic cells were also usually hypertrophic. The most severe examples of hyperplasia appeared as nodular growths with limited compression of the surrounding normal hepatic tissue. The minor lesions of degeneration, hepatitis, ductule cell proliferation, necrosis and focal lymphoid infiltration seen in the control animals and the T-I and T-1I groups are lesions of spontaneous disease and are not related to the Aroclor 1260. This level of liver disease is not unusual in old animals. Hyperplasia of the urinary bladder was found in an animal from the control group. This finding was not present in any of the rats fed Aroclor 1260. All of the other lesions in other tissues found in these animals are related to spontaneous disease and they are not unusual for old rats. Donovan E. Gordon, D. V. M. , Ph. D. Diplornate, American College of Veterinary Pathologists DSW 034181 STLCOPCB4018005 o TABLE XLin TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: Control Number of AnimalsOrgan Examined 11 Males Heart Trachea Lung Liver Stomach Spleen Kidney Testes " Prostate o U) Adrenal Gland X o Brain J" Eye CB ho Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal degeneration Ductile hyperplasia Chronic gastritis Hemosiderosis ' Chronic nephritis Testicular degeneration Periarteritis Inflammation Telangiectasis Nodular hyperplasia . Focal fatty change Focal encephalitis ' Inflammation Incidence 3 3 9 r 2 1 3 8 2 2 1 1 1 1 1 2 'PtuLtibunl B I O - T E S T Jaho'u ilo 'U&l, 9nc. Average Grade 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 ... o NJ a  . Pty-fstikial B I O - T E S T Jta b & 'ia la "uei, 9 hc. TABLE XLIH continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: Control Number of Animals Organ Examined Findings 14 Females ' o /) s: o OJ Heart Trachea Lung Liver Stomach Colon Spleen Ute rus Kidney Ovary Adrenal Gland Salivary Gland . Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal lymphoid infiltration Ductile hyperplasia Focal hepatitis Non-lipid vacuolar change Chronic gastritis Acanthosis - squamous epithelium Parasites . Hemosiderosis Metritis Chronic nephritis ' Focal lymphoid infiltration Cyst Telangiectasis Nodular hyperplasia Chronic fibrosis and atrophy All other tissues and organs were no rmal histologically. Grading System 0. 5 = minimal 2.0= mild 4. 0 = severe 1.0 = slight 3.0 = moderate 5. 0 = extreme Incidence 7 9 13 3 2 1 2 3 5 1 4 3 6 1 1 9 4 1_ " . Average Grade 2.0 1.0 1.0 1.0 1.0 1.0 0.5 1.0 1.0 1.0 1.0 2. 0 1.0 1.0 1.0 1. 0 1.0 1. 0 B I O - T E S T 2ab&uit<x'uc4, Sue. STLCOPCB4018008 Oo Number of Animals 11 Males O . </) 3C o OJ CD * TABLE XLIY TEST MATERIAL: Arodot 1260 Two-Year Chronic Oral Toxicity Study - Albino Rat3 Histopathologic Changes Final Sacrifice Group: 1 ppm ' Organ Examined Heart Trachea Lung Liver Pancreas Stomach Spleen Lymph Node Kidney Testes Prostate Seminal Vesicle Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal hepatitis Focal scarring Hemosiderosis Chronic focal pancreatitis Acute focal gastritis Hemosiderosis Congestion Chronic nephritis Testicular degeneration Periarteritis Inflammation Inflammation - Incidence 4 7 10 1. 1 1 2 .1 1 1 7 1 2 4 1 o Average Grade 1.0 1.0 2.0 1.0 1.0 1.0 ` 1.0 3.0 1.0 1.0 2.0 2.0 1.0 2.0 . 2.0 VJ e 1 j. Number of Animals 11 Males TABLE XL>rV continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 1 ppm ' Organ Examined Adrenal Gland Findings Nodular hyperoplasia Focal fatty change Incidence 2 2 DSW 14 Females o OJ 00 Ul Heart Trachea Lung Liver Stomach Chronic focal myocarditis . Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal fibrosis Focal lymphoid infiltration Ductile hyperplasia Congestion Vacuolar change (fatty) Chronic gastritis Acanthosis 3 1 9 13 1 1 1 1 1 1 2 o . Average Grade 1.0 1.0 1.0 3.0 1.0 1.0 1.0 1.0 0.5 1.0 2.0 1.0 1.0 wntyDiiyor i s a i o i a' Q TABLE XLIV continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 1 ppm ' Number of Animals__________ Organ Examined 14 Females Stomach Colon Spleen Lymph Node o Co Kidney ac o Uterus u> Adrenal Giand CD O' Findings Ulceration and acanthosis Parasites Hemosiderosis Hyperplasia Congestion Chronic nephritis Vacuolar change (fatty) Metritis Telangiectasis Nodular hyperplasia Congestion Incidence 1 1 11 1 1 3 1 4 9 3 1 O Average Grade 1.0 1.0 1.0 1.0 1.0 2.0 1.0 1.0 1.0 1.0 1.0 STLCOPCB4018010 All other tissues and organs were normal histologically. 0.5 = minimal 1.0= slight Grading System 2. 0 = mild 3. 0 = moderate 4. 0 = severe 5. 0 = extreme - -wu M STLCOPCB4018011 9 Number of Animals 7 Males TAB LE XLV TEST MATERIAL: Aroclor 1260 Two- Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice . Group: 10 ppm ' Organ Examined Heart Trachea Lung Liver Stomach ; Spleen Kidney Prostate Adrenal Gland Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease Suppurative pneumonia Vacuolar change (fatty) Chronic gastritis . Acanthosis Hemosiderosis Chronic nephritis Inflammation Nodular hyperplasia Incidence 3 2 5 1. 2 1 2 3 6 2 .1 14 Females </> O UJ - CD Heart Trachea Lung Chronic focal myocarditis Thracheitits Chronic respiratory disease 3 8 14 O Average Grade 1. 0 1. 0 1. 0 3. 0 1. 0 1. 0 1.0 1. 0 1. 0 1.0 . 1. 0 1.0 1.0 1.0 -4 0S-i\ JLS 3 1 O l 9 1D n u(!' ^ f 'W C . $(ubtit'uaL B IO - T E S T J.ahs'uiio-'iic i, Unc. e TABLE XLV continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: 10 ppm ' ['lumber of Average AnimalsOrgan ExaminedFindingsIncidenceGrade : males ooo SET O 00 CD Liver Pancreas Stomach Spleen Kidney Uterus Pituitary Adrenal Gland Vacuolar change (fatty) Focal hyperplasia Chronic focal pancreatitis Periarteritis Acanthosis Hemosiderosis Chronic nephritis Metritis Congestion Telangiectasis Nodular hyperplasia Congestion 1 1 1 1 1 12 10 7 1 7 1 1 1. 0 1.0 3. 0 3.0 1.0 . 1.0 .1.0 20 1. 0 1.0 1.0 1. 0 All other tissues and organs were normal histologically. . 5 = minimal . 0 = slight Grading System 2.0 = mild 3.0 = moderate 4. 0 = severe 5.0 = extreme -V4I NJ hJjuUial BIO-TEST Jlalfo'iak'iici, %tc. > v DO rg rt G43 .H D OOOOOOOOOO oooooo H H fvj *-- f\J --< fsj f~4 I-H *--< fS) *--< "H f-H r-* p>H 76 77 C a lcifie d concretions in pelvis 43 43 G 0o3 H 13 ,5 w 4-> rt I $ > fa X w o .5 rtfa >N 0 w 43 DO w rGt 43 j? o <D U H u *H o G oX DO O U rt fa i--4 o W >--rti (4 G rt CX +Oj to <x cx o o CX 0 o G O 43 to to do| Rl-l 03 C H Ut w rt a M 03 G 43 tHo 03 rt u o G O 4J G H rt u O to cx 10 43 rt R o 43 +3 DO rt RG rt 43 43 R U 43 43 CO CX O 4HJ 4GJ 43 GG 43 O & 43 rRt cx G to rt to rt s t~4 0 rt u o X-< >t-l G , DO O 42 4-> u H 43 r H rt} "M Hrt %u -H "l O <--i o M U DO 'H oG *43 rt G 3 to O o 'g 4M3 gc ^ to r-< H oa G oR 43 R O GG 43 43 43 O h DO p rt OR rOt OO 43 DO RO -Gt-* R 43 r rr-tt 43 y tG 43 ^ 68 03 O U O U > h U o fa U fa G rt V fa I o 03 43 B B rt 8 43 -M 43 M G O DO rt rt G rct DCi 43 G 0 X fa fa G 43 > r-4 fa oG r01t *Gw 43 u G rt 8g a to 5R 45 03 aa to to 43 Hrt DSW 034189 2 STLCOPCB4018013 Q Number of Animals 10 Males TABLE XLVI continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 100 ppm' Organ Examined Kidney (continued) Testes Prostate Thymus . Adrenal Gland Findings Calcified concretions in pelvis Aspermia Inflammation Cyst Telangiectasis Nodular hyperplasia Incidence 1 1 1 1. 3 1 15 Females Heart Trachea Lung o Co se Liver C/> o O O w S' 0 O o o 00 oU Chronic focal myocarditis Tracheitis Chronic respiratory disease Congestion - Edema Vacuolar change (fatty) 5 8 11 1 1 5 O to' 03 O m v Average Grade 1.0 1.0 1.0 1.0 1.0 1.0 a' r 1.0 1.0 1.0 1.0 1.0 1.0 -0 -a 9 Number of Animals 15 Females oCo s: o tO TABLE XLVI continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 100 ppm.' Organ Examined Liver (continued) . Pancreas Spleen Kidney Uterus Pituitary Adrenal Gland Parathyroid Findings Incidence Focal hyperplasia Chronic inflammation of liver capsule Centrolobular hypertrophy Necrosis Ductile cell hyperplasia, portal fibrosis and widespread eosinophil inclusions . in hepatocyte cytoplasm Chronic focal pancreatitis and periarteritis Hemosiderosis Chronic nephritis Metritis Congestion - Telangiectasis Nodular hyperplasia Congestion Hype rplasia 4 1 5 2, 1 1 9 8 7 1 6 1 1 1 All other tissues and organs were normal histologically. 0.5 = minimal Grading System 2. 0 = mild 4. 0 = severe Average Grade 1.0 1.0 1.0 2. 0 1.0 3.0 2. 0 1.0 1.0 1. 0 1.0 1.0 1.0 - -1.0 0B I T E S T X a h o 'ia k t' ic i, $nc. DtuiuiiAial B I O - T E S T Xak&'iaio'Uai, 9nc. 80 */ G. Detailed Description of Tumor Findings Tumor data for individual animals including location, weight and pathologic classification are presented in Tables XLVIII through LI. None of these tumors could be related to the ingestion of Aroclor 1260 and are considered normal for a random population of rats this age. t qSW 03^i-92 STLCOPCB4018016 D u d u ittia l B I O * T E S T Xaltotoioue-i., Dhc. STLCOPCB4018017 Animal Number and Sex 99-M 127-F 128-F 138-F 141-F 151 -F 152-F o v> s: oUJ sO Location Pituitary Pituitary Abdomen Pituitary Abdomen Abdomen Pituitary Ovary Abdomen Abdomen TABLE XLIX TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Group: 1 ppm Weight (grams) - 25.00 .60.80 20.07 14. 89 540.00 Size (cm) - 6x3x1 5x6x2 - '- 13 x 15 x 2 Classification Chromophobe adenoma Chromophobe adenoma Mammary fibroadenoma Chromophobe adenoma Mammary fibroadenoma Mammary fibroadenoma Chromophobe adenoma Adenoma Mammary fibroadenoma Mammary fibroadenoma Months on Test 20 24 21 24 24 24 22 a> tv & STLCOPCB4018018 Animal Number and Sex 205-F 208-F 213-F 216-F 220-F 221-F o Co O OJ vO Location Abdomen Pituitary Abdomen Right shoulder Abdomen Pituitary Submaxillary region Abdomen TABLE L TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Group: 10 ppm Weight (grams) ' 190.00 - .- . 138. 00 9. 57 - 14. 44 29. 0 Size (cm) 9x5x4 - Zx3x 1 3x5x2 Classification Mammary fibroadenoma Chromophobe adenoma Mammary fibroadenoma , Subcutaneous tumor Mammary fibroadenoma Chomophobe adenoma Fibroadenoma Mammary fibroadenoma Months on Test 24 24 24 23 24 24 oo w fvti.vpnvf'j- i s 1 " o i a iv>'qpr uc3 f Animal Number and Sex 7 22-F A 233-F 234-F TABLE L continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Description of Tumor Findings Group: 10 ppm Location Left femoral region Pituitary Abdomen Pancreas Weight _ (grams) 66.00 60. 82 * Size (cm) 6x8x2 6x4x3 Classification Subcutaneous tumor Chromophobe adenoma Mammary fibroadenoma Islet cell adenoma O m cr> Months on Test 6 24 24 STLCOPCB4018019 o </> o u.' 00 I-1 vO Ut Animal Number and Sex 244-M 264-M 281 -F 293-F 294-F 301 -F Location Pancreas Pancreas Abdomen Liver Abdominal cavity Liver TABLE LI TEST MATERIAL: Arodor 1260 Two-Year-Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Group: 100 ppm Weight (grams) - 35.04 50.75 Size (cm) - '- . - 6x4x2 6x4x3 Classification Adenoma Islet cell adenoma Mammary fibroadenoma Lymphos a rc oma Fibroma - - Lymphosarcoma o CO --I Ioo" O w *-> vD TJ O O DO oI* _i oo oIs) 4 00 O m to Months on Test 24 21 24 23 24 23 0U31 y i s a - o i ai Animal Numbe r and Sex 302-F 308-F 311-F 312-M 314-F Location Lymph node Pituitary Abdomen Pituitary Abdomen TABLE LI continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Group: 100 ppm Weight (grams) 14. 00 26.00 Size (cm) - - 4x3x2 1x2x1 - 5x4x3 Classification Lymphosarcoma Chromophobe adenoma Mammary fibroadenoma ; Mammary fibroadenoma Chromophobe adenoma Mammary fibroadenoma 3 Months on Test 24 24 24 24 24 o t/) X C/> o O UJ O 0 O DO *" vO "vJ o 0o0 Is) 0OO'